NEU3 sialidase strictly modulates GM3 levels in skeletal myoblasts C2C12 thus favoring their differentiation and protecting them from apoptosis.
Membrane-bound sialidase NEU3, often referred to as the "ganglioside sialidase," has a critical regulatory function on the sialoglycosphingolipid pattern of the cell membrane, with an anti-apoptotic function, especially in cancer cells. Although other sialidases have been shown to be involved in skeletal muscle differentiation, the role of NEU3 had yet to be disclosed. Herein we report that NEU3 plays a key role in skeletal muscle differentiation by strictly modulating the ganglioside content of adjacent cells, with special regard to GM3. Induced down-regulation of NEU3 in murine C2C12 myoblasts, even when partial, totally inhibits their capability to differentiate by increasing the GM3 level above a critical point, which causes epidermal growth factor receptor inhibition (and ultimately its down-regulation) and an higher responsiveness of myoblasts to the apoptotic stimuli.
Anastasia
Luigi
L
Department of Medical Chemistry, Biochemistry, and Biotechnology, University of Milan, 20090 Milan, Italy.
Papini
Nadia
N
Colazzo
Francesca
F
Palazzolo
Giacomo
G
Tringali
Cristina
C
Dileo
Loredana
L
Piccoli
Marco
M
Conforti
Erika
E
Sitzia
Clementina
C
Monti
Eugenio
E
Sampaolesi
Maurilio
M
Tettamanti
Guido
G
Venerando
Bruno
B
D000818:Animals; D017209:Apoptosis; D002454:Cell Differentiation; D002460:Cell Line; D015536:Down-Regulation; D004815:Epidermal Growth Factor / Q000037:antagonists & inhibitors / Q000378:metabolism; D066246:ErbB Receptors / Q000378:metabolism; D005679:G(M3) Ganglioside / Q000378:metabolism*; D020868:Gene Silencing; D006868:Hydrolysis; D051379:Mice; D008956:Models, Chemical; D018482:Muscle, Skeletal / Q000378:metabolism*; D009439:Neuraminidase / Q000378:metabolism*; D013107:Sphingolipids / Q000378:metabolism
D005679:G(M3) Ganglioside; D013107:Sphingolipids; D004815:Epidermal Growth Factor; D066246:ErbB Receptors; C511796:Neu3 protein, mouse; D009439:Neuraminidase